The overall long-term objective of the program is to gather an understanding of the mechanisms of and factors operating in cancer induction in the digestive organs. These studies are performed in model rodent systems with chemical carcinogens under experimental conditions which reliably lead to cancer in the esophagus, stomach, pancreas, and liver. These endeavors are integrated and multidisciplinary. The effect of modifying agents, such as enzyme inducers, or agents acting by other means of inhibition or enhancement, will be used to study in depth, with appropriate carcinogens, processes of cancer induction in the organs mentioned above. At the same time, utilizing labeled carcinogens or other suitable analytical technique, the effect of such pretreatment on the metabolism of the agents and their interaction with crucial tissue receptors will be examined, to delineate the specific reactions involved in carcinogenesis. In addition to in vivo studies, complementary experiments will be performed in vitro either with fractions of fresh tissues, or with cell systems in culture. The ability of various foods to support microorganisms capable of reducing nitrate to nitrite will be studied. In addition, experiments will be performed to determine if nitrosation of alkylamides and alkylamines can occur through catalysis by bacterial enzymes. Nitrosation in food whose pH has been lowered to simulate the gastric environment, and nitrosation in isolated rat stomach will also be studied. This set of experiments is designed to account for the occurrence of stomach and liver cancer in man.